Some patients with myeloma exhibit either acute or chronic deterioration of renal function in association with Bence Jones proteinuria (BJP). Chronic deterioration in renal function is often associated with distal tubule cast formation both in man and experimental mice. Our preliminary experimental data suggest that acute deterioration of renal function after administration of various BJP's to rats is partly a function of urine pH and isoelectric point (pI), it is not solely mediated by distal cast formation and is associated with a change in distal nephron water handling. Crystal formation in the proximal tubular epithelium on the other hand seems related to primary and secondary protein structure. It is proposed to characterize large numbers of Bence Jones proteins as to type, subtype, secondary structure (by circular dichroism) and pI and to examine the effect of administration of these proteins to maximally hydropenic Sprague Dawley rats and water loaded Brattleboro rats under conditions of aciduria and alkaluria. The studies will be done using an acute infusion model in the intact rat. It is also proposed to study the effects of inhibition of proximal light chain reabsorption by lysine on distal cast formation in the rat by immunohistologic and ultrastructural methods. Further in vitro studies are proposed to define crystallization conditions for 3 kappa1 light chains that form crystaline like structures in proximal tubular epithelium. It is hoped that these studies will further define mechanisms of both acute renal failure and chronic cast formation in patients with myeloma.